title: Serum IF1 concentration is independently associated to HDL levels and to coronary heart disease: the GENES study.
abstract: HDL is strongly inversely related to cardiovascular risk. Hepatic HDL uptake is controlled by ecto-F1-ATPase activity, and potentially inhibited by mitochondrial inhibitor factor 1 (IF1). We recently found that IF1 is present in serum and correlates with HDL-cholesterol (HDL-C). Here, we have evaluated the relationship between circulating IF1 and plasma lipoproteins, and we determined whether IF1 concentration is associated with the risk of coronary heart disease (CHD). Serum IF1 was measured in 648 coronary patients ages 45-74 and in 669 matched male controls, in the context of a cross-sectional study on CHD. Cardiovascular risk factors were documented for each participant, including life-style habits and biological and clinical markers. In controls, multivariate analysis demonstrated that IF1 was independently positively associated with HDL-C and apoA-I (r = 0.27 and 0.28, respectively, P < 0.001) and negatively with triglycerides (r = -0.23, P < 0.001). Mean IF1 concentration was lower in CHD patients than in controls (0.43 mg/l and 0.53 mg/l, respectively, P < 0.001). In multivariate analyses, following adjustments on cardiovascular risk factors or markers, IF1 was negatively related to CHD (P < 0.001). This relationship was maintained after adjustment for HDL-C or apoA-I. This study identifies IF1 as a new determinant of HDL-C that is inversely associated with CHD.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, 31000, France.
authors.forename: Annelise
authors.initials: A
authors.lastname: Genoux
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Ruidavets
authors.forename: Jean
authors.initials: J
authors.lastname: Ferrières
authors.forename: Guillaume
authors.initials: G
authors.lastname: Combes
authors.forename: Laeticia
authors.initials: L
authors.lastname: Lichtenstein
authors.forename: Véronique
authors.initials: V
authors.lastname: Pons
authors.forename: Muriel
authors.initials: M
authors.lastname: Laffargue
authors.forename: Dorota
authors.initials: D
authors.lastname: Taraszkiewicz
authors.forename: Didier
authors.initials: D
authors.lastname: Carrié
authors.forename: Meyer
authors.initials: M
authors.lastname: Elbaz
authors.forename: Bertrand
authors.initials: B
authors.lastname: Perret
authors.forename: Laurent O
authors.initials: LO
authors.lastname: Martinez
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D018570:Risk Assessment; D000097795:ATPase Inhibitory Protein
chemical_list: D015415:Biomarkers; D008075:Lipoproteins, HDL; D011506:Proteins; D000097795:ATPase Inhibitory Protein
keywords: ATP-synthase inhibitor factor 1; HDL-cholesterol; coronary heart disease; inhibitor factor 1; nucleotide receptor P2Y13